Researchers from the University of Bonn have identified a gene that can disrupt embryonic development and cause malformations.
An international study led by the Medical Faculty of the University of Bonn was able to locate a gene that plays an important role in the development of the human embryo. If this gene is altered malformations of various organ systems can occur.
The results have been published in the Journal of Medical Genetics.
Identifying the link between SHROOM4 and malformation
The researchers discovered the gene during a study of two individuals with congenital malformations.
“It was a man and his niece. Both had malformed kidneys, urinary tract and oesophagus, and the man also had a malformed right arm and heart,” explained Dr Gabriel Dworschak.
Physicians at the University Children’s Hospital in Bonn conduct
research on rare genetic diseases at the Institutes of Anatomy and Human
Genetics. When examining family members’ genetic makeup, they noticed an anomaly: a gene called SHROOM4 was altered in affected individuals compared to healthy individuals.
SHROOM4 was already familiar to the researchers from another context; the gene was known to play a key role in brain function. Mutations of this gene can lead to intellectual impairment, epileptic seizures, and behavioural abnormalities.
“Our findings indicated though, that it may play a broader role in embryonic organ development,” explained Dr Dworschak.
The team searched for other cases in which abnormalities in the SHROOM4 gene had also been found.
“Together with our cooperation partners, this led us to four more affected
individuals from three families. All of them had the SHROOM4 gene altered, but not always in the same way,” said Dr Heiko Reutter, from the University of Erlangen-Nuremberg.
This response did not clarify whether SHROOM4 variants were responsible for malformation in embryonic development. The researchers decided to test their hypothesis on an animal model. Zebrafish have a very similar gene to SHROOM4 which performs a similar function. Zebrafish larvae have transparent skin, making it easy for researchers to make observations under the light of a microscope.
Humans need SHROOM4 for healthy embryonic development
“Here at the University Hospital, we have the advantage that the research group led by Dr Benjamin Odermatt from the Institute of Neuroanatomy works a lot with zebrafish. This expertise came in handy in our study,” said Dr Caroline Kolvenbach, who was also involved in the study of SHROOM4.
The researchers almost completely inactivated the SHROOM4 gene in the larvae. The animals then showed malformations similar to those seen in human embryonic development. However, if larvae with deactivated SHROOM4 were injected with intact human genetic material, they developed almost normally.
“This shows first that they absolutely need a functional SHROOM4 for healthy embryonic development; and second, that the human gene can still take over the function of the fish gene,” Dr Dworschak explained.
The team now wants to find out which part the gene plays in embryonic
development.
“We assume that it is needed for very basic processes in the cell. It’s hard to explain otherwise why changes in the same gene cause such a variety of symptoms,” said Dr Dworschak.
